mRNA-transfected dendritic cell vaccination in high risk uveal melanoma patients

Patients with uveal melanoma will be initially treated locally (for example
with enucleation of the effected eye), after which there is frequently a
complete remission. Especially in the patient group with chromosomal
abnormalities (eg loss of chromosome 3) a large group will develop metastases.
An effective treatment for metastasized melanoma is not available. Standard
treatment with chemotherapy is effective in only a very limited number of
patients and is not lasting. In large studies treatment with chemotherapy did
not shown a survival benifit.
In previous studies we have treated stage III and IV melanoma patients with
mature dendritic cells loaded with tumor-specific antigens. We have shown that
this approach is feasible, and leads to very limited toxicity.
In this study we will treat 30 patients with DC electroporated with mRNA coding
for gp100 and tyrosinase. The vaccinations will be given intravenously and
intradermally. A group of 30 patients who fulfill all inclusion criteria except
for HLA-A2 phenotype, and therefore receive no vaccinations, will serve as a
control.

The primary goal is to show the capability of monocyte-derived DC after RNA
electroporation for melanoma antigens to induce an immune response.
The secondary objective is to show clinical response.

This is a two-armed study including two times 31 patients. Arm A will be
treated with 3 DC vaccinations at 2 week interval. In case of response the
procedure can be repeated to boost the immune response. Arm B will receive the
standard treatment (observation).

Arm A will be vaccinated with DC vaccine, intravenous and intradermal 3 times
with 2 week intervals.

The burden and risk associated with participation can be considered minimal.
Previous studies (200+ patients treated in our centre) showed that toxicity was
limited to local reactions at the site of injection, activation of the immune
system (elevated temperature, flu-like symptoms), furthermore a limited group
showed allergic skin reactions and depigmentation of the skin.
Apheresis is a safe procedure. Patients will have to visit our outpatient
clinic (aferese, vaccination 1-3, skin test), extra blood will be drawn
(vaccination 2 and 3 and skin test). Furthermore patients will undergo a skin
test by which 6 mm biopsies will be taken.